tbuckley/cabot-search huggingface dataset:
Comparison of 5- and 10-year breast cancer risk predictions.
Authors: John L. Hopper, Gillian S. Dite, Erika Leigh Spaeth Tuff
Journal: Journal of Clinical Oncology (2023)

10529 Background: Breast cancer risk assessment is valuable in personalizing risk-reduction and screening approaches for the general population. Maximizing the benefits while reducing the harms associated with current breast cancer screening and risk-reduction recommendations should increase the efficacy of these paradigms. Because healthcare providers have limited time with their patients, we developed a risk prediction model, BRISK, which uses the most important clinical risk factors for breast cancer (in an easily collected format), polygenic risk and mammographic density. We previously validated BRISK 5-year risk predictions and found that it performed better than IBISv7 and BCRAT. Methods: The dataset comprised 241,633 women (mean age at baseline assessment = 56.6 years). We included all races/ethnicities available in the UK Biobank. There were 3726 women affected during the first five years of follow-up and 7482 women affected during the full 10 years of follow-up. We compared the performance of the 5-year and 10-year risk predictions by assessing the association with breast cancer using Cox regression to estimate the hazard ratio (HR) per SD of risk, discrimination using calculating Harrell’s C-index and calibration using logistic regression to estimate the slope and the intercept of the logit of the risk predictions. Nelson–Aalen estimates of the hazard function by quintiles of risk and standardized incidence ratios (SIRs) of the number of breast cancer cases expected were used to illustrate performance. Results: The predictive performance of BRISK was consistent for 5-year and 10-year risk predictions. Discrimination was similar, with a Harrell’s C-index of 0.645 (95% CI = 0.636, 0.654) for the 5-year risk and of 0.638 (95% CI = 0.632, 0.645) for the 10-year risk. We used Nelson_Aalen cumulative hazard estimates to compare breast cancer incidence by risk quintile for both 5 and 10-year risk. Both risk scores overestimated risk in the top two deciles with the 5-year expected risks of 2.8% and 5.0% corresponding to observed risks of 2.3% and 3.3%. The 10-year expected risks for the top two deciles were 5.6% and 9.8% while the corresponding observed risks were 4.6% and 6.4%. Finally, we used clinically actionable thresholds to show the standard incidence ratios (SIR) of 1.77 (95% CI = 1.69, 1.85) for women ≥3% 5-year risk and 2.05 (95% CI = 1.93, 2.18) ≥8% 10-year risk. Conclusions: The BRISK 5-year and 10-year risk prediction perform equally well. There is an overestimation of risk for the top decile in both models. This is important to consider in risk-management conversations between clinician and patient. While the observed risk of the top decile remained above the 3% 5-year risk threshold used in the United States, the top decile observed risk dropped below the 8% 10-year risk threshold used in the United Kingdom. Risk scores are not used in isolation, but it may be preferable to err on the side of overestimation rather than underestimation.
Translational development of BAFF-R-specific chimeric antigen receptor T-cell therapy targeting B-cell lymphoid malignancies.
Authors: Yan Luo, Yaqing Qie, Martha E. Gadd, Alak Manna, Tommy To, Shuhua Li, Hemant S. Murthy, Roxana Stefania Dronca, Mohamed Kharfan-Dabaja, Hong Qin
Journal: Journal of Clinical Oncology (2023)

e19501 Background: Relapsed and/or refractory (R/R) disease is observed in patients who receive CD19 targeting chimeric antigen receptor (CAR)-T cells to treat B-cell lymphoid leukemias and lymphomas. We generated a novel CAR, MC10029 that targets B-cell activating factor receptor (BAFF-R) to address this unmet medical need. Methods: We engineered a second-generation BAFF-R CAR (MC10029 CAR). The construct includes the single chain variable fragment (scFv) of our newly developed BAFF-R antibody with CD28 costimulatory and CD3ζ signaling domains. We confirmed MC10029 CAR-T cell antigen-specific activation with in vitro degranulation assays and a direct cytolytic assay. We used BAFF-R positive leukemia and lymphoma cell lines in both in vitro and in vivo models to further characterize MC10029 CAR-T cells, and finally, we enriched tumor primary cells from chronic lymphocytic leukemia (CLL) patients as a target for MC10029 CAR-T cells. In preparation for our Phase I clinical trial, we have manufactured three batches of CAR-T cells using a MC10029-encoding lentiviral vector produced under GMP conditions. The production batches of MC10029 CAR-T cells were evaluated for product quality with Viability, Identity and Potency as well as Safety from adventitious viral agents. Antigen specific cytotoxicity of the MC10029 CAR-T cells was confirmed using our standard degranulation assay. Results: MC10029 CAR-T cells elicited in vitro antigen-specific cytotoxicity against Nalm-6 cells, Z138 cells, MEC-1 cells, and a CD19 knock out Nalm-6 model designed to mimic CD19-negative R/R disease. We demonstrated in vivo antitumor effects of MC10029 CAR-T cells in NSG mice challenged with these same cell lines. We showed cytotoxicity of MC10029 CAR-T cells against CLL patients’ tumors. We also showed our quality control results to highlight our clinical trial trajectory. Conclusions: Novel MC10029 CAR-T cells showed broad utility against BAFF-R positive B-cell lymphoid malignancies in a series of in vitro, in vivo, and ex vivo models. With these robust data, we have moved forward to generate clinical grade MC10029 CAR-T cells using cGMP manufacturing and quality protocols in preparation of a MC10029 CAR-T cell Phase I clinical trial.
An intersectional approach to cervical cancer screening disparities by race/ethnicity and immigrant status.
Authors: Jane J. Chen, Indra N. Sarkar, Emily Hsu, Don S. Dizon
Journal: Journal of Clinical Oncology (2023)

6536 Background: Racial/ethnic minority and immigrant groups individually experience lower rates of cervical cancer (CC) screening. Although immigrants represent large proportions of racial/ethnic minorities, few studies have explored the interacting health consequences of these social categories. Intersectionality is a theoretical framework which recognizes that studying social categories independently cannot capture their cumulative effects on health. In the context of CC screening, only one study took this approach but did not analyze several important barriers to care. This study aims to analyze the joint influence of race/ethnicity and immigrant status on screening and identify barriers unique to each intersectional group. Methods: Data from the National Health Interview Survey years 2005, 2010 and 2015 were drawn from IPUMS. Analyses were restricted to those eligible for CC screening (n=17,941). Multivariable logistic regression was used to model the interactional effect of race/ethnicity and immigrant status on screening up to date (UTD) status adjusting for confounders. Variables reflecting socioeconomic status (SES), access to care, acculturation and language were separately included to see whether they explained identified disparities. Finally, amongst women not UTD on screening, reasons for this were analyzed. All analyses were adjusted for complex survey design. Results: US born Non-Hispanic Black women had higher odds of being UTD on screening (OR 1.63, 95% CI [1.23, 2.18]) while immigrant Non-Hispanic White (OR 0.45 [0.29, 0.7]), immigrant Asian (OR 0.29 [0.2, 0.42]) and immigrant Hispanic/Latinx women (OR 0.51 [0.39, 0.67]) had lower odds compared to US born Non-Hispanic White women. Adjusting for SES (OR 0.87 [0.65, 1.16]) and access (OR 1 [0.74, 1.36]) attenuated the ORs for immigrant Hispanic/Latinx women but not immigrant Asian and White women. Adjusting for acculturation attenuated the ORs for immigrant Hispanic/Latinx (OR 0.84 [0.58, 1.22]) and White women (OR 0.68 [0.42, 1.12]) only. Adjusting for language increased but did not attenuate the ORs for all immigrant groups. Analyses of reasons for not screening showed immigrant Non-Hispanic White, Black and Asian women had greater proportions selecting “Didn’t need or know needed this test” versus other groups (10-12% vs. 5.4-8.4%). Conclusions: Immigrant status continues to explain much of the CC screening disparities previously attributed to race/ethnicity. SES and access to care remain important barriers for immigrant Hispanic/Latinx women but less so for other immigrant groups. This study reveals that acculturation is an important barrier for immigrant Non-Hispanic White and Hispanic/Latinx women, possibly representing disparities in knowledge. Language barriers may also contribute in all immigrant women. Further intersectional studies are needed to identify remaining barriers.
Quality and accessibility of liquid biopsy information: An analysis of online content.
Authors: Henry Kazunaru Litt, Emma Greenstreet Akman, Evelin Trejo, Narjust Florez, Ana I. Velazquez Manana
Journal: Journal of Clinical Oncology (2023)

11010 Background: Circulating tumor DNA assays, also known as liquid biopsies, are increasingly used by oncologists to evaluate residual disease, cancer genomic composition, resistance mechanisms, and guide therapy selection. Since patients often use the internet as a source of medical information, we evaluated the quality, accessibility, and understandability of publicly available online information on liquid biopsies. Methods: We performed a cross-sectional study of 100 videos and 100 webpages that resulted from the search of “liquid biopsy” on a commonly used search engine (Google) and social network (YouTube). Videos over 5 min, scientific articles, and non-English content were excluded. Videos were evaluated for content, intended audience, and perceived sex and race/ethnicity of speakers. Two independent reviewers evaluated understandability and quality of health information using two validated tools for consumer health information (PEMAT, DISCERN). Any disagreements were resolved by a 3rd independent reviewer. Webpages were evaluated for accessibility (use of visual aids, other languages), quality of information (authors, citations, indications, limitations, cost), reading level, and presence of commercial bias. Reading level was evaluated using the validated Flesch-Kincaid (FK), Gunning Fog (GF), and SMOG indices. Data was summarized with descriptive statistics. Results: We reviewed 100 videos, with 190 median views per video (IQR: 75-719). Most videos were intended for a scientific audience (72%) and lacked diversity of speakers. The majority of featured speakers were perceived as male (65%) and non-Hispanic white (72%). Overall, liquid biopsy videos were complex and low quality. Only 9% of videos were understandable and 8% presented moderate to high quality health information. Furthermore, we reviewed 100 webpages about liquid biopsies; key characteristics are summarized in the table. About a third of webpages included indications (36%) and limitations (35%) of liquid biopsies. Webpages had a median text reading level of 14.1 (IQR: 12.1-15.8), 16.4 (IQR: 14.4-18.6), and 15.9 (IQR: 13.9-16.9) based on FK, GF, and SMOG indices, respectively. Only 2 websites had one index reading level of 8 th grade or lower as recommended by the NIH and CDC. Conclusions: Online content about liquid biopsies is complex and requires education levels exceeding the reading level of the general US population. Extensive shortcomings in sources of unbiased and understandable information for patients with cancer exist. As novel diagnostic technologies and treatments emerge, efforts should be made to develop understandable, unbiased, and high-quality information resources for patients with cancer. Characteristics of liquid biopsy webpages. [Table: see text]
Association of frailty index of laboratory tests (FI-LAB) and COVID-19 clinical outcomes in veterans with cancer.
Authors: Natasha Melo Resendes, Ekta Panjrolia, Toufic Tannous, Armando Sarasua, Jorge G. Ruiz, Krystal Hasel, Janaki Neela Sharma, Iriana M. Hammel
Journal: Journal of Clinical Oncology (2023)

e24023 Background: Veterans with cancer have high COVID-19-attributable mortality. Frailty, a multisystem syndrome characterized by vulnerability to stressors from loss of physiological reserve, is common in cancer patients and confers worse clinical outcomes. In hospitalized cancer patients with COVID-19 infection, the role of frailty remains unclear. Our study aim was to compare clinical and utilization outcomes of cancer patients hospitalized with COVID-19 according to frailty status. Methods: The retrospective cohort study included hospitalized veterans with cancer and acute COVID-19 infection at 7 VA facilities in Florida and Puerto Rico from March-August 2020. Frailty was assessed using a 31-item frailty index of laboratory tests and vital signs (FI-LAB) with scores grouped by tertiles. We chart reviewed VA databases to collect Veterans’ socio-demographics, COVID-19 Polymerase Chain Reaction (PCR) results, and clinical and utilization outcomes. We ran binomial logistic regression analyses to calculate the odds of inpatient death, ICU admission, ICU transfer, prolonged length of stay, new nursing home placement, 30-day readmission, 30-day mortality, 6-month,1-year, and 2-year mortality according to the tertiles, adjusted for age, BMI, sex, race, ethnicity, and other conditions with greater risk for poor COVID-19 outcomes. Patients were followed until death or August 13, 2022. Results: 143 older Veterans with cancer were hospitalized with a mean age of 74.4 years (SD = 11.5) years, 95.9% (n = 117) male, 66.4% white (n = 81), and 9.8% (n = 12) Hispanic. 122 (85.3%) met the inclusion criteria. There were no differences in baseline sociodemographic or clinical characteristics except for a higher prevalence of congestive heart failure. The upper FI-LAB tertile had a higher risk of inpatient death, OR 12.47 (95%CI:1.3-121.4), p = 0.03, 30-day post-discharge mortality, OR 9.78 (95%CI:.21-79.4), p = .03 and 2-yr post-discharge mortality OR 4.9 (1.2-19.6) p &lt; 0.03. There were no differences in other clinical and utilization outcomes. Conclusions: In hospitalized Veterans with cancer and coexistent COVID-19 infection, patients with higher levels of frailty have a greater risk of inpatient death, 30-day post-discharge mortality, and 2-year post-discharge mortality. More studies are needed to confirm the utility of FI-LAB in hospitalized patients with COVID-19 and cancer.
Digital cancer genetic risk assessment in a gynecologic oncology clinic.
Authors: Emily M. Webster, Muhammad Danyal Ahsan, Luiza Perez, Leslie Bull, Laura Keenahan, Sarah R. Levi, Shannon M. Kieran, Evelyn Cantillo, Eloise Chapman-Davis, Kevin Holcomb, Ravi N. Sharaf, Melissa Kristen Frey
Journal: Journal of Clinical Oncology (2023)

10612 Background: Population-based screening for hereditary cancer syndromes and referral of those who screen positive for genetic testing is a cost effective, evidence-based national health priority. However, under-recognition of hereditary cancer syndromes remains a critical concern, with fewer than 20% of individuals with Hereditary Breast and Ovarian Cancer Syndrome and Lynch Syndrome identified. Here, we evaluate the Ambry Genetics Comprehensive, Assessment, Risk, and Education (CARE) Program, a risk-stratification tool to assess eligibility for National Comprehensive Cancer Network (NCCN) genetic testing criteria and lifetime risk for breast cancer based on the Tyrer-Cuzick (version 8.0) risk algorithm. Methods: Between November 2022 and February 2023, new patients in a gynecologic oncology clinic were prompted by text message to complete CARE prior to their appointment. Those using CARE then completed a System Usability Scale (SUS), a validated 10-item questionnaire for the assessment of perceived usability. Results: Sixty patients presented for a new patient gynecologic oncology appointment and were prompted to complete CARE. The median patient age was 55 years (interquartile range, 40-68). The patients self-identified as Non-Hispanic White (44, 73%), Non-Hispanic Black (5, 8%), Asian (5, 8%), Hispanic (3, 5%), other (2, 3%), and unknown (1, 2%). All identified as female. Forty-three patients (72%) completed CARE. Among CARE users, 11 (26%) were identified as meeting criteria for genetic testing; of these, 9 (82%) proceeded with point-of-care same day genetic testing. Nine (21%) patients were eligible for enhanced breast cancer screening based on an estimated lifetime breast cancer risk of 20% or greater; of these, 100% were referred for high-risk breast screening. There were no patient demographics associated with completion of CARE. Forty-one patients (72%) completed the SUS survey; the median SUS score was 80 (interquartile range, 60-92.5), which corresponded to 85-89th percentile and a letter grade of A-. Conclusions: Implementation of a digital tool for cancer genetic risk assessment identified a quarter of patients to be eligible for genetic testing, among whom 82% completed same-day genetic testing. Additionally, the tool was reviewed favorably by patient users. Large randomized controlled trials of health information technology tools are needed to move closer to the goal of population-based hereditary cancer risk assessment.
A phase Ib/II study of GFH018 in combination with toripalimab in recurrent/metastatic nasopharyngeal carcinoma (R/M NPC).
Authors: Hai-Qiang Mai, Ye Guo, Muh-Hwa Yang, Kunyu Yang, Li-Tzong Chen, Hui Mun, Yan Yang, Shuang Wang, Huaqiang Zhu, Haige Shen, Yu Wang
Journal: Journal of Clinical Oncology (2023)

6026 Background: The transformed growth factor beta (TGF-β) signaling pathway is dysregulated in carcinogenesis. In NPC patients, upregulation of TGF-β pathway is correlated with disease stage or phenotype due to Epstein-Barr virus (EBV) infection. GFH018, a novel TGF-βRI inhibitor, can inhibit tumor growth through inhibiting the activity of TGF-βRI kinase to block the signal transduction of TGF-β and modulate the tumor immune microenvironment. Preclinical studies showed that GFH018 in combination with PD-1/PD-L1 monoclonal antibody can significantly inhibit tumor growth synergistically. Here we report the preliminary results of combining GFH018 and Toripalimab treating R/M NPC patients (pts). Methods: This is a phase Ib/II study to evaluate the safety and efficacy of the combination of GFH018 and Toripalimab in pts with advanced solid tumors. Patients with RM NPC were enrolled to receive GFH018 80mg twice a day (BID) 14-day-on/14-day-off in combination with Toripalimab 3mg/kg every two weeks. Tumor assessment was performed every 8 weeks per Response Evaluation Criteria in Solid Tumor (RECIST) 1.1. Results: As of 31 Dec 2022, 32 pts with R/M NPC who had progressed on at least one prior line therapy were enrolled. Sixteen (50%) had received ≥3 lines of prior therapies, and 19 (59.4%) had previously received immune checkpoint inhibitors (ICIs) and platinum-based chemotherapies. The median duration of study drug exposure was 7 weeks. Twenty-five pts (78.1%) experienced treatment-related adverse events (TRAEs) of any grades, and 11 pts (34.4%) had ≥ Grade 3. The most common TRAEs (occurring in ≥ 3 pts) were anaemia (n = 6, 18.8%), hyponatraemia (n = 6, 18.8%), rash (n = 6, 18.8%), fatigue (n = 4, 12.5%), white blood cell count decreased (n = 4, 12.5%), aspartate aminotransferase increased (n = 3, 9.4%), back pain (n = 3, 9.4%), decreased appetite (n = 3, 9.4%), hypokalaemia (n = 3, 9.4%), and hypothyroidism (n = 3, 9.4%). As of 18 Jan 2023, among the 27 pts with post-baseline tumor assessments, 8 achieved partial response (PR), and 5 stable disease (SD); the overall response rate (ORR) was 29.6%, and disease control rate (DCR) was 48.1%. Six PR and 2 SD were observed among the 12 pts without prior treatment of ICIs; the ORR was 50%, and DCR was 66.7%. Four pts discontinued treatment without any post-baseline tumor assessments due to AEs or withdrawal of consent, and 1 patient is premature for tumor assessment. Conclusions: GFH018 combined Toripalimab was well tolerated and demonstrated preliminary efficacy in pts with R/M NPC. Specifically, in pts who had not previously received ICIs, promising antitumor activity was observed supporting further investigation to this group of pts. Clinical trial information: NCT04914286 .
Prospective observational study to evaluate lemborexant utility in insomnia among women with breast cancer (WJOG14921B, LUNAR study).
Authors: Yukinori Ozaki, Mari Hosonaga, Manabu Futamura, Sasagu Kurozumi, Takuma Onoe, Tsutomu Iwasa, Hidenori Kamio, Kaori Terata, Rurina Watanuki, Hiroko Masuda, Yoshinori Saeki, Shigehisa Kitano, Kentaro Sakamaki, Kiyomi Nonogaki, Yuta Yoshimura, Daisuke Kawai, Toshimi Takano
Journal: Journal of Clinical Oncology (2023)

TPS12148 Background: Insomnia occurs in approximately 60% of cancer patients. The importance of early intervention to treat insomnia has been advocated because insomnia may be associated with poor prognosis, early discontinuation of treatment and decreased quality of life. It has been reported that breast cancer patients receiving endocrine therapy have the highest rate of insomnia among all cancer patients due to vasomotor symptoms (ie, hot flashes) and comorbid symptoms associated with fatigue and depression. Insomnia has also been found to occur in patients with metastatic/recurrent breast cancer. Lemborexant (LEM) is a dual orexin receptor antagonist, which has been shown to be effective for insomnia patients without malignancies. In clinical practice, while LEM has been administered to cancer patients with insomnia, there are no prospective data. The aim of this study is to evaluate prospectively whether LEM improves insomnia in patients with breast cancer receiving endocrine therapy. Methods: This is an open-label, prospective, multicenter, observational study to evaluate efficacy and safety of LEM to treat insomnia in patients with breast cancer receiving endocrine therapy [UMIN000047718]. The primary endpoint is change from baseline of total Insomnia Severity Index (ISI) score at 1 month. Secondary endpoints include change from baseline of cancer fatigue scale scores, EORTC QLQ C-30 and BR23 score, and Patient Health Questionnaire-9 score after 1 month and 3 months, change from baseline in total sleep time and sleep efficiency using an electronic sleep diary after 2 weeks, 1 month and 3 months, and safety profile. Exploratory endpoints include biomarker analysis including evaluation of cytokines and orexin A levels, and evaluation of sleep parameters using Oura ring, which is a ring-type wearable device. The primary endpoint will be assessed by the Wilcoxon signed-rank test. Total sample size will be 70 patients (adjuvant cohort: 50 patients, recurrent and/or metastatic cohort: 20 patients). Patients ≥20, meeting Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition for Insomnia Disorder and ISI score ≥10 will be eligible. LEM 5mg will be administrated orally every night. Dosage of LEM will follow clinical practice and the Japanese LEM label. Enrollment began in September 2022; 14 patients have been recruited in adjuvant cohort as of January 2023. Clinical trial information: UMIN000047718 .